The first chapter explains the origins of the time machine later used by the Otherhood. Caspar Last has created a time machine primarily as a solution for a mathematical riddle, rather than the desire to make use of it. He is well aware of the theory on the hazards of time travel, and seeks to avoid these. Specifically, Last is aware that the present to which the traveler returns "is not truly the one from which he departed". Even a slight and cautious use of the technology has caused a ripple effect in the fabric of time. Therefore, Last determines to make one use and one only of his invention: to travel to 19th Century British Guiana, make himself wealthy by obtaining a very rare stamp, and thereafter never use time travel or let it be used by others. However, the Otherhood think otherwise; having found out about Last's invention, they buy his stamp, take the technology over and embark on very intensively using time-travel to preserve the peace of the world and the existence of the British Empire, aims which they consider to be virtually synonymous.

The second chapter concerns a timeline in which the British Empire has survived as a dominant world power throughout the Twentieth Century. The main character, Denys Winterset, a promising young official in the Colonial Service at Africa in the 1950s, is invited to join a secret society which has the ability to alter time. This society, which calls itself the Otherhood, was originally endowed by Cecil Rhodes in 1893 to preserve and expand the British Empire.

Invited to the Otherhood's secret headquarters, located out of normal time and space, Winterset is told that there had been "An Original Situation", whose description suggests our own familiar history. There, what Winterset knew as the six-month-long "War of 1914" had degenerated into a mass four-year-long bloodletting (i.e. the First World War), followed by the rise of various dictatorships and tyrannies, more terrible wars and unimaginable mass murders, and finally the development of terrible destructive weapons capable of utterly destroying the world. The calamity also involved the complete dissolution of the British Empire, which Winterset regards as the main guarantor of the world's peace and stability.

This "Original Situation" had been slowly and carefully averted by the ability of the Otherhood's agents to go back in time, change the past, and create the peaceful, British-dominated world which Winterset had hitherto taken for granted. However, in the Otherhood's timeless headquarters, all this is still to be done.

Then Winterset is told that there is a vital role for him to play which no one else can fulfill: he must travel back to the beginning of the group in 1893 and assassinate Rhodes. Otherwise, in the late 1890s Rhodes would change his will and dissipate much of his fortune, the Otherhood would never come into being, and the terrible nightmare of the Twentieth Century would be restored.

At this point, the story line leaves the young Winterset and shifts to the President pro tem, who is later revealed to be a different manifestation of Winterset and who travels into the future, something previously outlawed by the Otherhood. There, he learns that the far future is not at all what they aimed for or sought to create. In fact, it is a weak fabric, constantly changing and fluctuating. There is a "capital of an aged empire" which bears only a vague resemblance to London; the street plans, the systems of communications and public transportation, the orthography of books, are all constantly changing and shifting - in random response to some change made in time past by the Otherhood - and the new reality seems to have "always been there" but the President also retains the memory that but a short time ago it was different.

Moreover, there is a far more fundamental change - the world is no longer inhabited by a single intelligent race, but by many: several races of worker "hominidae" and reptilian "draconidae" personal servants; true humans; long-lived, wise "magi"; and the mysterious "sylphidae" or "angels". The President thinks that, to effect such a change in evolution itself, somebody must have traveled a million years into the past - though the Otherhood always took care never to go earlier than 1893, so as not to risk annulling itself.

The Magi and Angels, however, explain to him it is not so: no one had gone so far into the past, no one intentionally interfered with evolution. Rather, the Otherhood's excessive tinkering with the timelines has generated countless unintended changes. These accumulated exponentially across time and thus created this future world. And while the lower hominids and draconids are unaware of the ongoing changes, the Magi have inferred their existence during "hundreds of years of pondering" which they know to have been "imaginary centuries". They are tormented by this knowledge, to the point that they long to die, to never have been and to put an end to this imaginary existence. They are also foresee the inevitable future rise of the lizard 'draconids' race, leading to a total collapse of civilisation and the reversion of the world to one of unchanging forest and water.

For their part, the race of Angels feel acute pain at any new change, "like the snap of a whip infinitely long" - starting from the very moment when they felt themselves come into being "Oldest of the Old Races, though the last which the Otherhood's changes brought into being". They know their future, too - unbearably, they know that the rate of random changes will become worse and worse, and that this world, which they love, is doomed to "sicken and fail". Therefore, they charge the President pro tem to "put out this world like a light". He must go back, prevent Winterset (who is himself) from killing Rhodes - and thereby annul the Otherhood, destroy this alternate history which the Otherhood brought into being, and restore the "true" Original Situation. Crying bitterly, the President sees no choice but to do it.

Meanwhile, a younger Winterset has arrived in 1893 Cape Town and has no difficulty in gaining the trust of Cecil Rhodes, as he exactly fits the type of young man Rhodes likes to have about him (which is why the Otherhood chose Winterset for the job). But at the moment of opportunity - when Rhodes trustingly turns his back in the night, and Winterset could shoot him and make good his escape - Winterset fails to pull the trigger, due to some kind of an outside interference. (Winterset dimly remembers an apparition appearing during his sleep - evidently the older Winterset/President pro tem using some kind of future-hypnosis). Winterset's failure to act has immediate, far-reaching and irreversible results: Rhodes survives, the Otherhood is therefore never formed, and there is no backup team with a time-machine to take Winterset back to the future - indeed, the future he came from no longer exists. Winterset is trapped in the past, enters the service of Rhodes and witnesses first-hand the ugly and brutal side of Rhodes's independent colony-building - very far from Winterset's idea of the British Empire in which he grew up. Later on, Winterset can only watch helplessly as "The Original Situation" reasserts itself, the world is convulsed by two World Wars and the second one is followed by the breakup of the British Empire.

In the final chapter, Winterset, a young man, now living in the "true" twentieth century history, enters the Colonial Service though it is a doomed institution with the Empire's colonies being ceded to new independent nations in Africa. He meets his older self in 1956 in Africa and learns of the truth of time-travel. He helps his older self to escape from Africa amid the chaos, and returns to London, where the story ends with their last meeting many years later.

Winterset notes in the Times newspaper "the sale of the single known example of the 1856 magenta British Guiana" stamp, known to have been owned in 1956 by the Otherhood, and Winterset states that he realises that time-travel means that all the narrative sequence of his story is still vulnerable to being re-written by time-travel.

'Great Work of Time' has the same basic outline as Isaac Asimov's The End of Eternity - i.e. a secret society of well-meaning time travelers bent on remodeling history, and a young man recruited into the society in order to make a specific change that would bring this society itself into being. The details of what the time travelers do and where in time they operate are much different from those in Asimov's book. However, in both books, the society's operations come to a halt through the influence of people from the future, because the society's actions endanger the existence of the future.